LncRNA PCAT-1 upregulates RAP1A through modulating miR-324-5p and promotes survival in lung cancer.

Abstract

IntroductionLung cancer is the malignant tumor with the fastest increase in morbidity and mortality and the greatest threat to human health and life. Long non-coding RNA (lncRNA) is emerging as an important regulator in many cancers. Recently, it was found that lncRNA prostate cancer associated transcript 1 (PCAT-1) was up-regulated in lung cancer, playing oncogenic roles. However, the underlying regulatory mechanism of PCAT-1 remains unknown.Material and methodsThe expression levels of PCAT-1 and miR-324-5p were analyzed by real-time PCR, and RAP1A expression was determined by western blotting. RNA pull-down, luciferase and western blotting assays were used to examine the target relationship between PCAT-1 and miR-324-5p or that between miR-324-5p and RAP1A. The functional effects of PCAT-1 and miR-324-5p were examined using cell viability and cell apoptosis assays.ResultsPCAT-1 overexpression remarkably promoted cell proliferation and suppressed cell apoptosis. Mechanistic investigations demonstrated that PCAT-1 can interact with miR-324-5p and repress its expression, thereby increasing the expression of its target RAP1A. Additionally, rescue experiments revealed that PCAT-1 served as an oncogene partly through sponging miR-324-5p and upregulating RAP1A in lung cancer cells.ConclusionsOur findings demonstrate that on account of the dual function of pro-proliferation and anti-apoptosis, PCAT-1/miR-324-5p/RAP1A may be novel candidates for application in the diagnosis, prognosis and therapy of lung cancer.